Notice of Special Interest (NOSI): Chronic Inflammation of the Oral Cavity - An Agent for Oral Mucosal Disease

Application Due Date
Brief Description

The National Institute of Dental and Craniofacial Research (NIDCR) is issuing this Notice of Special Interest (NOSI) to encourage research studies that investigate the mechanisms of chronic inflammation of the oral cavity, including chronic oral manifestations of systemic diseases. Chronic inflammation of the oral mucosa can create or contribute to serious health conditions within and outside the oral cavity. This announcement encourages studies with a mechanistic focus on chronic inflammation as they relate to onset or progression of dental, oral and craniofacial diseases. 

Multiple inflammatory mechanisms may lead to a state of chronic inflammation within the oral cavity including those initiated by commensal or pathogenic microbiota, or through host immunity and mucosal homeostasis disruption. While it is recognized that oral chronic inflammation is associated with a variety of systemic conditions, the mechanisms by which chronic inflammation then affects the onset and progress of diseases of the oral cavity is less clear. Commensal microbiota are known to affect inflammation and other mechanisms that play a role in carcinogenesis. In the context of plasminogen deficiency, commensal organisms can trigger extravascular fibrin deposition in the oral mucosa, leading to tissue damage and chronic inflammation.Elevated levels of oral Fusobacterium nucleatum are linked to extraoral cancer locations, such as the gut tract. F. nucleatum has also been associated with oral inflammation and poor survival in early-stage HPV-negative tongue cancer.  

Viral infections can amplify or worsen chronic inflammation and can lead to various autoimmune related conditions. Amplified innate and adaptive immune responses observed following antigen exposure support a role for infections driving the immunopathology and acting as environmental risk factors, possibly involving molecular mimicry in immune hyperactivity. This is reported in some individuals following infection with SARS-CoV-2, where some patients develop multiple types of autoantibodies and autoimmune disease. As another example, active Epstein-Barr virus (EBV) infection is selectively associated with ectopic lymphoid structures in the salivary glands of Sjögren Disease patients and appears to contribute to local growth and differentiation of disease-specific autoreactive B cells. Immune responses of treatment-naïve patients diagnosed with Sjögren Disease to an H1N1 influenza vaccine identified a mechanistic basis for the B cell hyperactivity. Chronic inflammation can also be associated with oral mucosal autoimmunity in the absence of viral infection like Crohn’s disease, Lupus, and leukemias can present as chronic oral inflammation.  Chronic oral inflammation can be associated with food intolerance, chronic fungal infection as in erythematous candidiasis, and environmental factors like smoking and alcohol use.